Growth, patterning and cellular differentiation are inextricably linked during development, but what coordinates these processes? To find out, ten Berge and colleagues have been studying how the skeletal core, connective tissues and muscles of the vertebrate limb develop from a proliferating mass of mesenchymal cells. On , they report that Wnt and FGF signals coordinate growth with lineage specification during limb development. FGFs from the apical ectodermal ridge (AER) of the limb bud and Wnts from the AER and the surface ectoderm,they report, act synergistically to promote proliferation and maintain the limb mesenchymal cells in an undifferentiated state, but act separately to specify cell lineages. Thus, withdrawal of both signals causes cell-cycle withdrawal and chondrogenic differentiation, whereas Wnt exposure alone maintains proliferation and favours connective tissue differentiation. The authors incorporate these results into a new model for limb development in which localized Wnt and FGF signals coordinate growth, patterning and cellular differentiation, and guide the growing limb's spatial organization.
